This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS: 1. To compare differences in sleep macro- and microarchitecture in rheumatoid arthritis patients and healthy controls. Previous investigations have found evidence of disordered sleep in rheumatoid arthritis, independent of the contribution of evening pain (Drewes et al. 1998). We will extend prior studies that have relied on traditional visual stage scoring, use computer analysis of sleep EEG, and provide a more complete description of brain activity during sleep in rheumatoid arthritis patients and controls. 2. To determine the association between sleep and morning levels of pro-inflammatory cytokine expression and daytime symptoms of morning stiffness, fatigue and pain. Upon waking, circulating levels and stimulated expression of IL-6 and TNF will be examined in both rheumatoid arthritis and healthy control subjects. Furthermore, for rheumatoid arthritis subjects, relationships between sleep and symptoms such as joint stiffness and pain and overall fatigue will be assessed. 3. To establish the predictive validity of pro-inflammatory cytokines for disordered sleep in rheumatoid arthritis. We will evaluate whether the expression of pro-inflammatory cytokines prior to sleep onset predicts sleep amount and depth, independent of evening pain, in both rheumatoid arthritis and healthy control groups. In addition, subsequent sleep assessments with the rheumatoid arthritis subjects will be conducted in which a TNF antagonist will be administered to experimentally probe the action of nocturnal pro-inflammatory cytokines on sleep quality and depth. TNF antagonism decreases biologically available TNF and serum levels of IL-6 (Feldmann and Maini 1999).